ArticleThe Journal of biological chemistry2018
Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.
- Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.Nature communications · 2020Pooled it
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- AMPK promotes TFEB transcriptional activity through dephosphorylation at both MTORC1-dependent and -independent sites.Autophagy · 2026Article
- Review
- Review
- Multi-Omic, Multi-Tissue Responses to Acute Exercise in Sedentary Adults: Findings from the Molecular Transducers of Physical Activity Consortium.bioRxiv : the preprint server for biology · 2026Article
- Substrate-selective mTORC1 regulation and gene dosage-dependent tissue divergence in Birt-Hogg-Dubé syndrome.Frontiers in oncology · 2026Review
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Differential contribution of TFE3 isoforms to cell motility and invasion.EMBO reports · 2026Article
- TFEB and MCOLN1 are important forFrontiers in cellular and infection microbiology · 2026Article
- MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma.Cell reports · 2025Article
- PPP2/PP2A-mediated dephosphorylation of LC3B links PINK1-PRKN/Parkin-mediated mitophagy to SCA12 pathogenesis.Autophagy · 2025Article
- cAMP promotes acute lysosome biogenesis through TFEB nuclear import-export dynamics.bioRxiv : the preprint server for biology · 2025Article
- Quantum sensing of free radicals in macrophages reveals early autophagy-lysosome regulation in an atherosclerosis cell model.Redox biology · 2025Article
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
- The PP2A-B55α phosphatase is a master regulator of mitochondrial degradation and biogenesis.Science advances · 2025Article
- TFEB and TFE3 regulate STING1-dependent immune responses by controlling type I interferon signaling.Autophagy · 2025Article
- Article
- TFEB-mediated proinflammatory response in murine macrophages induced by acute Alpha7 nicotinic receptor activation.Journal of leukocyte biology · 2025Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Adaptations and responses to stress conditions are fundamental processes that all cells must accomplish to maintain or restore cellular homeostasis. Cells have a plethora of response pathways to mitigate the effect of different environmental stressors. The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. Therefore, understanding their regulation under different stress conditions is of great interest. Here, using a range of human and murine cells, we show that TFEB and TFE3 are activated upon induction of acute oxidative stress by sodium arsenite via an mTOR complex 1 (mTORC1)-independent process. We found that the mechanism of arsenite-stimulated TFEB and TFE3 activation instead involves protein phosphatase 2A (PP2A)-mediated dephosphorylation at Ser-211 and Ser-321, respectively. Depletion of either the catalytic (PPP2CA+B) or regulatory (PPP2R2A/B55α) subunits of PP2A, as well as PP2A inactivation with the specific inhibitor okadaic acid, abolished TFEB and TFE3 activation in response to sodium arsenite. Conversely, PP2A activation by ceramide or the sphingosine-like compound FTY720 was sufficient to induce TFE3 nuclear translocation. MS analysis revealed that PP2A dephosphorylates TFEB at several residues, including Ser-109, Ser-114, Ser-122, and Ser-211, thus facilitating TFEB activation. Overall, this work identifies a critical mechanism that activates TFEB and TFE3 without turning off mTORC1 activity. We propose that this mechanism may enable some cell types such as immune or cancer cells that require simultaneous TFEB/TFE3 and mTORC1 signaling to survive and achieve robust cell growth in stressful environments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.